The K23 candidate (Ellen Fung, PhD RD) is an Assistant Research Scientist with advanced training in nutrition and a long- standing interest in the impact of nutrition on children with chronic disease. This application describes a comprehensive, interdisciplinary program that builds upon the candidate's strengths to provide the skills and experience necessary for her development into an independent clinical investigator. The candidate's primary mentor, Elliott Vichinsky, MD is an internationally recognized expert in hematology who has mentored numerous candidates towards their success as independent clinical scientists. The proposed scientific advisory committee will consist of a team of highly qualified experts in the fields of study: zinc and bone metabolism and biostatistics. The primary aim of this study is to determine if zinc supplementation improves bone health in young patients with beta-Thalassemia. Osteoporosis is a significant co-morbidity in patients with thalassemia which leads to decreased quality of life. The most effective way to prevent osteoporosis is to build strong, dense bones in the early years. A combination of disease, endocrine and nutritional factors likely contribute to the etiology of osteoporosis in this population. However, even well transfused patients with normal gonadal function who are supplemented with calcium have low bone mass. It is hypothesized that patients with beta-Thalassemia have low bone mass, in part, due to zinc deficiency. Sub-optimal zinc status has been identified in patients with thalassemia and zinc supplementation has been shown to improve linear growth. To test the primary hypothesis, a 24 month randomized placebo-controlled trial of zinc supplementation (25 mg Zn/day) plus usual care therapy (calcium + vitamin D) vs. usual therapy alone will be conducted in 60 young patients (9-25 yrs) with beta-Thalassemia and low bone mass (spine BMD Z-score <-1.0). Bone health, as estimated from measurements of bone mass (by DXA and QCT) and markers of bone formation and resorption will be the primary outcome variables. The secondary aim will evaluate zinc homeostasis in a sub-sample of subjects at baseline and following 6 months of zinc supplementation through the use of compartmental models of zinc metabolism. This will be the first study to examine the effects of zinc supplementation on bone health in patients with beta-Thalassemia. If zinc supplementation is found to have a clinically important effect, this simple, safe, non-invasive therapy could quickly become a part of the standard care of these young patients and improve overall health in children and adult patients with beta-Thalassemia.